System of electrospray ion generator

ABSTRACT

This invention relates to an analytical instrument field, specifically an instrument for pharmaceutical micromolecular and biological macromolecular ion generation. By this invention, through a hollow capillary emission needle and an emission needle bracket, the emission needle bracket forms a forward moving laminar flow gas surrounding the emission needles, eliminating the capillary counter-flow effect outside the capillary for liquid flowing out of the hollow capillary emission needle and pushing liquid forward; and vacuum lead-in capillary whose entrance is a specially designed arc mechanism, makes zero air flow speed in any direction, and the entrance happens to be the exit of the hollow capillary emission needle so as to ensure steady Taylor cone on the tip edge and ultimately obtains steady ion flow within a large flow range. This invention has advantages of steady ion emission and high ion transmission efficiency, and can be widely applied in the ion source preparation.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an analytical instrument field, specifically an instrument for pharmaceutical micromolecular and biological macromolecular ion generation.

2. Description of the Related Art

It has been two decades since John B. Fenn, one of the laureates of Nobel Prize in Chemistry for 2002, applied Electrospray Ion (ESI) source to macromolecular mass spectrometry in the mid 1980s, but the ESI source mechanism still stays in two models: Ion Evaporation Model (IEM) and Charged Residue Model (CRM). The basic structure of ESI source has no essential difference with that in the 1990s.

The basic structure of ESI source is filling a hollow metal or glass capillary tube with liquid against the ion inlet of the mass spectrum, applying positive or negative high voltage to the liquid, wherein positive and negative ions are formed in the atmosphere, and the vacuum system of the mass-spectrograph absorbs some of ions into the mass analyzer of the mass-spectrograph.

For the ESI source, although the ionization probability is so high as to almost reach 100%, effective ions which transfer molecular ions to the MS (mass spectrum) mass detector range from 0.01% to 0.1% of the total number of ions.

To solve the aforementioned problem, many inventors discovered ESI sources of different mechanisms, in which their reference patent numbers are U.S. Pat. No. 4,861,988, U.S. Pat. No. 5,412,208, U.S. Pat. No. 5,432,343, U.S. Pat. No. 6,992,299 and U.S. Pat. No. 5,504,329. However, all of these prior inventions put the emission needle of the ESI source in the air. As the ion flow and the liquid flow are closely related, steady ion emission cannot be obtained within a large flow range of 100 nl/min-200 ul/min and there are no substantial improvements in the ion transmission efficiency by these prior arts.

SUMMARY OF THE INVENTION

An object of the invention is to overcome at least some of the drawbacks relating to the prior arts as mentioned above.

Against existing technical shortcomings, the present invention proposes a highly efficient, rationally designed, structurally simple instrument with high ionization probability and steady ion emission.

The objective of the present invention is to provide a rationally designed, structurally simple ESI source with high ionization probability and steady ion emission.

The objective of the present invention is realized by the application of the following technical scheme: It includes hollow capillary emission needle; emission needle brackets which form a forward moving laminar flow gas surrounding the emission needle, eliminating the capillary counter-flow effect outside the capillary for liquid flowing out of the hollow capillary emission needle and pushing liquid forward; vacuum lead-in capillary whose entrance is a specially designed arc mechanism, making zero air flow speed in any direction, and the entrance happens to be the exit of the hollow capillary emission needle so as to ensure steady Taylor cone on the tip edge of emission needle and ultimately obtain steady ion flow within a large flow range.

The present invention is realized by the application of the following technical scheme:

An ESI generator, which includes a hollow capillary emission needle, an HV terminal, a hollow capillary emission needle bracket, and its features are:

One edge of the fixed block is located in the forepart of the HV terminal cavum and there is a through-hole in the middle of the fixed block.

The connecting pipe of the liquid chromatography passes through the through-hole in the fixed block and is fixed in the HV terminal, and exterior wall of the connecting pipe of the liquid chromatography fits tightly the interior wall of the through-hole in the fixed block to ensure that air will not leak from the tightly fit location and flow in another direction.

The vacuum lead-in capillary and the HV terminal connect through the hollow capillary emission needle bracket whose one edge is embedded into the HV terminal cavum and whose other edge is embedded into the vacuum lead-in capillary cavum, thus forming a connection.

The middle of the hollow capillary emission needle bracket is a through cavum, which fits the forepart cavum diameter of the hollow capillary emission needle bracket and the hollow capillary emission needle diameter and prevents air from flowing in this direction but keeps it flowing in an even more spacious direction.

The rear cavum diameter of the hollow capillary emission needle bracket is more than 1.1 times the hollow capillary emission needle diameter so that air may flow in this direction, and the forepart cavum is less than the rear cavum. There are a number of side holes in the side of the hollow capillary emission needle connecting the rear cavum.

The bottom of the vacuum lead-in capillary cavum is a curved surface, and there is an aperture between the bottom and the edge of the hollow capillary emission needle bracket to further ensure the gap and not to form a sealed construction.

There are gas cavities on the side of the vacuum lead-in capillary which pass through the side hole of the hollow capillary emission needle so as to lead in external air.

The hollow capillary emission needle and the vacuum lead-in capillary are on the same axis, and the hollow capillary emission needle point is above the end plane of the hollow capillary emission needle bracket.

Preferably, the HV terminal cavum in the aforementioned ESI generator is large at the ends and small in the middle, and the liquid chromatography connecting pipe joins the hollow capillary emission needle bracket at the middle section of the HV terminal cavum.

Preferably, there are auxiliary bores and air holes at the side of the vacuum lead-in capillary of the aforementioned ESI generator, and auxiliary bores and air holes run through the cavum.

As a better choice, there are 1-16 auxiliary bores and gas cavities each in the side of the vacuum lead-in capillary of the aforementioned ESI generator, and in application, 4-8 auxiliary bores are generally selected for better economic benefits and technical effects.

Preferably, 1˜16 side bores in the side of the hollow capillary emission needle bracket of the aforementioned ESI generator run through the rear cavum.

Preferably, the hollow capillary emission needle point in the aforementioned ESI generator goes beyond the end plane of the hollow capillary emission needle bracket within a range of 5 mm. This is the specific choice technique made based on technical features of the present invention, and there are certainly better effects than existing technology beyond the aforementioned 5 mm, including leveling with the end plane which generates very good effects.

Preferably, gases which run through the auxiliary bores and cavities in the aforementioned ESI generator are nitrogen, oxygen, argon, hydrogen, air or mixture of the same gases. As a better choice, argon or air is selected from the aforementioned gases.

Preferably, the hollow capillary emission needle in the aforementioned ESI generator is hollow glass capillary or hollow metal capillary. As a better choice, the outlet of the same hollow capillary emission needle is needle-like hollow glass capillary or hollow metal capillary, and specific features of the present invention will highlight technical effects of the present invention.

Preferably, the vacuum lead-in capillary in the aforementioned ESI generator is of metal material, glass material or ceramic material.

Preferably, the hollow capillary emission needle, vacuum lead-in capillary, liquid chromatography connecting pipe, vacuum lead-in capillary, HV terminal and hollow capillary emission needle bracket are on the same axis.

Preferably, the other edge of the vacuum lead-in capillary in the aforementioned ESI generator connects the mass spectrograph.

Beneficial effects: Compared with the background technology of the prior arts, rational design of the present invention puts the emission needle point and vacuum lead-in capillary on the same axis properly, adopts new air flow design, ensures the zero gas flow at the outlet of the hollow capillary emission needle.

Rational design of the vacuum lead-in capillary enables ion cluster of fan-shaped emission to focus on the center of the vacuum lead-in capillary and leads ions into the mass spectrograph. The present invention has advantages of steady ion emission and high ion transmission efficiency and it is a fairly ideal ESI source.

In conclusion, the key merits of the present invention comprise:

A system of an Electrospray Ion (ESI) generator including a hollow capillary emission needle, a HV (high-voltage) terminal and a hollow capillary emission needle bracket comprises the following parts, components and processes:

-   -   a) One edge of a fixed block is located in the forepart of the         aforementioned HV terminal cavum and there is a through-hole in         the middle of the aforementioned fixed block,     -   b) A connecting pipe of a liquid chromatography passes through         the aforementioned through-hole in the aforementioned fixed         block and is fixed in the aforementioned HV terminal, and         exterior wall of the aforementioned connecting pipe of the         aforementioned liquid chromatography fits tightly the interior         wall of the aforementioned through-hole in the aforementioned         fixed block,     -   c) A vacuum lead-in capillary and the aforementioned HV terminal         connect through the aforementioned hollow capillary emission         needle bracket whose one edge is embedded into the         aforementioned HV terminal cavum and whose other edge is         embedded into the aforementioned vacuum lead-in capillary cavum,         thus to form a connection,     -   d) The middle of the aforementioned hollow capillary emission         needle bracket is a through cavum which fits the forepart cavum         diameter of the aforementioned hollow capillary emission needle         bracket and a hollow capillary emission needle diameter, while         the rear cavum diameter of the aforementioned hollow capillary         emission needle bracket is more than 1.1 times of the         aforementioned hollow capillary emission needle diameter, and         the aforementioned forepart cavum is less than the         aforementioned rear cavum, wherein there is a number of side         holes in the side of the aforementioned hollow capillary         emission needle connecting the aforementioned rear cavum,     -   e) The bottom of the aforementioned vacuum lead-in capillary         cavum is a curved surface, and there is an aperture between the         bottom and the edge of the aforementioned hollow capillary         emission needle bracket, wherein there is gas cavities on the         side of the aforementioned vacuum lead-in capillary passing         through the side hole of the aforementioned hollow capillary         emission needle, and     -   f) The aforementioned hollow capillary emission needle and the         aforementioned vacuum lead-in capillary are on the same axis,         and the aforementioned hollow capillary emission needle point is         above the end plane of the aforementioned hollow capillary         emission needle bracket.

The aforementioned HV terminal cavum is large at the ends and small in the middle, and the aforementioned liquid chromatography connecting pipe joins the aforementioned hollow capillary emission needle bracket at the middle section of the aforementioned HV terminal cavum.

The aforementioned vacuum lead-in capillary has auxiliary bores and gas cavities, and the aforementioned auxiliary bores and the aforementioned gas cavities are through-connected with the aforementioned cavum.

There are 1˜16 auxiliary bores and gas cavities, as set forth above, each in the side of the aforementioned vacuum lead-in capillary.

The aforementioned 1˜16 side bores in the side of the aforementioned hollow capillary emission needle bracket run through the aforementioned rear cavum.

The aforementioned hollow capillary emission needle point goes beyond the end plane of the aforementioned hollow capillary emission needle bracket within a range of 5 mm.

The aforementioned gases which run through the aforementioned auxiliary bores and the aforementioned gas cavities are nitrogen, oxygen, argon, hydrogen, air or mixture of the aforementioned gases.

The aforementioned hollow capillary emission needle is hollow glass capillary or hollow metal capillary.

The outlet of the aforementioned hollow capillary emission needle is needle-like hollow glass capillary or hollow metal capillary.

The aforementioned vacuum lead-in capillary is of metal material, glass material or ceramic material.

The aforementioned hollow capillary emission needle, the aforementioned vacuum lead-in capillary, the aforementioned liquid chromatography connecting pipe, the aforementioned HV terminal and the aforementioned hollow capillary emission needle bracket are on the same axis.

The aforementioned other edge of the aforementioned vacuum lead-in capillary connects a mass spectrograph.

All these and other introductions of the present invention will become much clear when the drawings as well as the detailed descriptions are taken into consideration.

BRIEF DESCRIPTION OF THE DRAWINGS

For the full understanding of the nature of the present invention, reference should be made to the following detailed descriptions with the accompanying drawings in which:

FIG. 1 is the section view diagram of the present invention.

FIG. 2 is the structural schematic diagram of the vacuum lead-in capillary of the present invention.

FIG. 3 is the illustrative diagram of heated capillary gas flow of the present invention.

FIG. 4 is the section view diagram of application structure of the present invention.

FIG. 5 is the structural schematic diagram of the hollow capillary emission needle bracket of the present invention.

FIG. 6 is the schematic diagram for the connection of application device of the present invention.

FIG. 7 is the test data diagram I.

FIG. 8 is the test data diagram II.

Like reference numerals refer to like parts throughout the several views of the drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention will be described more fully hereinafter with reference to the accompanying drawings, in which some examples of the embodiments of the invention are shown. Indeed, the present invention may be embodied in many different forms and should not be construed as limitation to the embodiments set forth herein, rather, these embodiments are provided by way of example so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout.

The following specification for the implementation of the present invention is made based on the attached drawings.

EXAMPLE 1

Based on the structure demonstrated by FIG. 1, FIG. 2, FIG. 4 and FIG. 5, an ESI generator is made, including the hollow capillary emission needle, HV terminal, hollow capillary emission needle bracket, one edge of the fixed block located on the cavum forepart of the HV terminal, and there is a through-hole in the middle of the fixed block; liquid chromatography connecting pipe runs through the through-hole in the fixed block and is fixed in the HV terminal, and the exterior wall of the liquid chromatography connecting pipe fits well the interior wall of the through-hole of the fixed block; the vacuum lead-in capillary connects the HV terminal through the hollow capillary emission needle bracket whose one edge is embedded into the cavum of the HV terminal and whose other edge is embedded into the cavum of the vacuum lead-in capillary, forming connection; the middle of the hollow capillary emission needle bracket is a through cavum, the diameter at the forepart cavum embedded with the HV terminal matches with the diameter of hollow capillary emission needle; the rear cavum diameter of the hollow capillary emission needle bracket is more than 1.2 times the hollow capillary emission needle diameter, and there are a number of side holes in the side of the hollow capillary emission needle connecting the rear cavum; the bottom of the vacuum lead-in capillary cavum is a curved surface, and there is an aperture between the bottom and the edge of the hollow capillary emission needle bracket; there are pores on the side of the vacuum lead-in capillary which pass through the side hole of the hollow capillary emission needle; the hollow capillary emission needle and the vacuum lead-in capillary are on the same axis, the hollow capillary emission needle point is above the end plane of the hollow capillary emission needle bracket; the HV terminal cavum is large at the ends and small in the middle, the liquid chromatography connecting pipe joins the hollow capillary emission needle bracket at the middle section of the HV terminal cavum.

Then, based on the structure demonstrated by FIG. 6, it connects the aforementioned ESI generator with mass spectrograph, gas conduit, liquid chromatography separation column, ESI source, liquid chromatography, HV power supply and HV auxiliary gas cylinder into a whole.

The hollow capillary emission needle is inserted into the vacuum lead-in capillary, liquid flows into the hollow capillary emission needle through the liquid chromatography connecting pipe, the vacuum system of the mass spectrograph, through the vacuum lead-in capillary, forms an auxiliary air flow surrounding the hollow capillary emission needle between the hollow capillary emission needle and the hollow capillary emission needle bracket, as set forth above, when high voltage is applied to the HV terminal, and a Taylor cone is formed at the top of the hollow capillary emission needle, the emission fan-shaped ion cluster at the top of the Taylor cone, due to the gas suction effect of the mass spectrograph, a rotating air flow is formed on the surface of the vacuum lead-in capillary, and the ion focus at the vacuum lead-in capillary center is sent into the mass spectrograph, as shown in FIG. 4.

FIG. 3 is the illustrative diagram of the implementation of the present invention.

Liquid chromatograph flow is 50 ml/min, sample size is 100 femtomoles, and femtomole is a measuring unit, sample is Sigma's Angiotensin III, mass spectrum is Thermo LCQ ion well. Data in FIG. 7 was obtained from tests.

FIG. 7 shows the present invention's result at its upper part and the conventional ESI source result at the lower part. The figure shows the signal intensity increases twice, and the SNR (signal noise rate) is around 30 times of the conventional ESI source.

Liquid chromatograph flow is 200 nl/min, sample size is 50 femtomoles, sample is US Michrom's enzymolysis bovine albumin, mass spectrum is Thermo LCQ ion well. Data in FIG. 8 was obtained from tests.

FIG. 8 shows the total ion trajectory of mass spectrum at its upper part and the highest ion peak trajectory at the lower part. FIG. 8 shows no interruption occurs in either of the two ion trajectories during the 75-min analysis, indicating the ion flow is very stable and the conventional ESI source is completely unreachable and impossible.

EXAMPLE 2

Given the same structure as in Example 1, there are auxiliary bores in the side of the vacuum lead-in capillary, the auxiliary bores run through the cavum; there are four auxiliary bores in the side of the vacuum lead-in capillary, gas which runs through auxiliary bores is nitrogen; the hollow capillary emission needle point goes beyond the end plane of the hollow capillary emission bracket by 2 mm; the hollow capillary emission needle is hollow glass capillary; the vacuum lead-in capillary is metal material, then the hollow capillary emission needle, the vacuum lead-in capillary, liquid chromatograph connection pipe, the vacuum lead-in capillary, the HV terminal and the hollow capillary emission bracket are put on the same axis; the rear cavum diameter of the hollow capillary emission bracket is 1.3 times the diameter of the hollow capillary emission needle; liquid chromatograph flow is 50 ml/min, sample size is 100 femtomoles, sample is Sigma's Angiotensin III, mass spectrum is Thermo LCQ ion well, the experiment results approach FIG. 7, with good technical effects.

EXAMPLE 3

Given the same structure as in Example 1, there are auxiliary bores in the side of the vacuum lead-in capillary, the auxiliary bores run through the cavum; there are eight auxiliary bores in the side of the vacuum lead-in capillary, gas which runs through auxiliary bores is air; the hollow capillary emission needle point goes beyond the end plane of the hollow capillary emission bracket by 5 mm; the hollow capillary emission needle is hollow metal capillary; the vacuum lead-in capillary is ceramic material, then the hollow capillary emission needle, the vacuum lead-in capillary, liquid chromatograph connection pipe, the vacuum lead-in capillary, the HV terminal and the hollow capillary emission bracket are put on the same axis; the rear cavum diameter of the hollow capillary emission bracket is 1.4 times the diameter of the hollow capillary emission needle; liquid chromatograph flow is 200 nl/min, sample size is 50 femtomoles, sample is US Michrom's enzymolysis bovine albumin, mass spectrum is Thermo LCQ ion well, the experiment results approach FIG. 8, with good technical effects.

When auxiliary gas applied in the present invention is mixture of the aforementioned gases, it generates the same good technical effects and results.

The system and method of the present invention are not meant to be limited to the aforementioned experiment, and the subsequent specific description utilization and explanation of certain characteristics previously recited as being characteristics of this experiment are not intended to be limited to such techniques.

Many modifications and other embodiments of the present invention set forth herein will come to mind to one ordinary skilled in the art to which the present invention pertains having the benefit of the teachings presented in the foregoing descriptions. Therefore, it is to be understood that the present invention is not to be limited to the specific examples of the embodiments disclosed and that modifications, variations, changes and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. 

1. A system of an Electrospray Ion (ESI) generator including a hollow capillary emission needle, a HV (high-voltage) terminal and a hollow capillary emission needle bracket, said system comprising: a) One edge of a fixed block located in the forepart of said HV terminal cavum and there being a through-hole in the middle of said fixed block, b) A connecting pipe of a liquid chromatography passing through said through-hole in said fixed block and fixed in said HV terminal, and exterior wall of said connecting pipe of said liquid chromatography fitting tightly the interior wall of said through-hole in said fixed block, c) A vacuum lead-in capillary and said HV terminal connecting through said hollow capillary emission needle bracket whose one edge being embedded into said HV terminal cavum and whose other edge being embedded into said vacuum lead-in capillary cavum, thus to form a connection, d) The middle of said hollow capillary emission needle bracket being a through cavum which fits the forepart cavum diameter of said hollow capillary emission needle bracket and a hollow capillary emission needle diameter, while the rear cavum diameter of said hollow capillary emission needle bracket being more than 1.1 times of said hollow capillary emission needle diameter, and said forepart cavum less than said rear cavum, wherein there existing a number of side holes in the side of said hollow capillary emission needle connecting said rear cavum, e) The bottom of said vacuum lead-in capillary cavum being a curved surface, and there being an aperture between the bottom and the edge of said hollow capillary emission needle bracket, wherein there existing gas cavities on the side of said vacuum lead-in capillary passing through the side hole of said hollow capillary emission needle, and f) Said hollow capillary emission needle and said vacuum lead-in capillary being on the same axis, and said hollow capillary emission needle point being above the end plane of said hollow capillary emission needle bracket.
 2. A system as recited in claim 1, wherein said HV terminal cavum is large at the ends and small in the middle, and said liquid chromatography connecting pipe joins said hollow capillary emission needle bracket at the middle section of said HV terminal cavum.
 3. A system as recited in claim 1, wherein said vacuum lead-in capillary has auxiliary bores and gas cavities, and said auxiliary bores and said gas cavities are through-connected with said cavum.
 4. A system as recited in claim 3, wherein there are 1˜16 said auxiliary bores and said gas cavities each in the side of said vacuum lead-in capillary.
 5. A system as recited in claim 4, wherein said 1˜16 side bores in the side of said hollow capillary emission needle bracket run through said rear cavum.
 6. A system as recited in claim 1, wherein said hollow capillary emission needle point goes beyond the end plane of said hollow capillary emission needle bracket within a range of 5 mm.
 7. A system as recited in claim 1, wherein said gases which run through said auxiliary bores and said gas cavities are nitrogen, oxygen, argon, hydrogen, air or mixture of said gases.
 8. A system as recited in claim 7, wherein said gases which run through said auxiliary bores and said gas cavities are nitrogen or air.
 9. A system as recited in claim 1, wherein said hollow capillary emission needle is hollow glass capillary or hollow metal capillary.
 10. A system as recited in claim 9, wherein the outlet of said hollow capillary emission needle is needle-like hollow glass capillary or hollow metal capillary.
 11. A system as recited in claim 1, wherein said vacuum lead-in capillary is of metal material, glass material or ceramic material.
 12. A system as recited in claim 1, wherein said hollow capillary emission needle, said vacuum lead-in capillary, said liquid chromatography connecting pipe, said HV terminal and said hollow capillary emission needle bracket are on the same axis.
 13. A system as recited in claim 1, wherein said other edge of said vacuum lead-in capillary connects a mass spectrograph. 